Port and related container system

ABSTRACT

A container system includes a flexible bag, a probe port, and a probe. The probe port includes an elongated tubular member having an interior surface bounding a first passageway extending between a first end and an opposing second end, the tubular member being made of a polymeric or elastomeric material and being flexible. The probe port also includes a flange coupled to the tubular member and radially outwardly projecting therefrom, the flange being secured to the flexible bag so that the first end of the tubular member projects into a chamber of the flexible bag while the second end of the first passageway of the tubular member is accessible from outside of the flexible bag. The probe can be received within the first passageway of the probe port.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/645,549, filed Jul. 10, 2017, which is a continuation of U.S. patentapplication Ser. No. 14/450,102, filed Aug. 1, 2014, U.S. Pat. No.9,726,551, which is a divisional of U.S. patent application Ser. No.13/013,479, filed Jan. 25, 2011, U.S. Pat. No. 8,794,825, which is adivisional of U.S. patent application Ser. No. 12/357,817, filed Jan.22, 2009, U.S. Pat. No. 7,878,079, which is a divisional of applicationSer. No. 11/385,626 filed on Mar. 20, 2006, U.S. Pat. No. 7,487,688,which are incorporated herein by specific reference.

BACKGROUND OF THE INVENTION 1. The Field of the Invention

The present invention relates to container systems having a probe portfor receiving a probe.

2. The Relevant Technology

Ports are a necessary feature of bioreactors for delivering controlledvolumes of gas, liquid, or other material to growth media containingcells; for extracting matter out of the bioreactor; and for insertingprobes, such as a temperature probe, to monitor conditions within thebioreactor. Conventional ports comprise tubular metal or hard plasticstems that are permanently attachable to the bioreactor container.Various tubes or probes are then attached to the ports or are passedthrough the ports. In all embodiments, great care is taken so that noleaking or contamination occurs at the ports.

Although conventional ports are useful for their intended purpose asdetailed above, they have a number of shortcomings. For example, becauseconventional ports typically are made of metal or hard plastic, theports are typically rigid and inflexible. Because of this inflexibility,it can be difficult to establish a seal around tubes or other structuresthat are passed through the ports. As a result, an unwanted dead spacecan be formed between the ports and the structures passing therethrough.

Furthermore, the inflexibility of conventional ports can cause problemswhen used with flexible containers. An advantage of using flexiblecontainers is that the containers can be folded up for transport orstorage when not in use, making the stored containers more compact,easier to handle, and requiring less room to store. Rigid ports decreasethe flexibility of the containers and increase the risk that the portscould damage the containers when the containers are folded around theports.

Sampling from bioreactors typically occurs by simply connecting asampling tube to a corresponding port and withdrawing the sampletherefrom. This sampling technique typically withdraws the sample fluidfrom the perimeter of the container. Such a sample, however, may bemisrepresentative of the typically more homogeneous fluid that iscontained closer to the center of the container.

Accordingly, what are needed are improved ports that overcome one ormore of the above problems or other shortcomings known in the art.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be discussed withreference to the appended drawings. It is appreciated that thesedrawings depict only typical embodiments of the invention and aretherefore not to be considered limiting of its scope.

FIG. 1 is a cross sectional side view of a containment system havingmultiple tube ports and a sampling port;

FIG. 2 is a perspective view of one of the tube ports of the containmentsystem depicted in FIG. 1;

FIG. 3 is a cross sectional side view of a portion of the tube portshown in FIG. 2, showing an annular lip seal;

FIG. 4 is a cross sectional side view of the tube port shown in FIG. 2with a temperature probe inserted therein;

FIG. 5 is a cross sectional side view of the tube port shown in FIG. 2connected to a fluid line via a connector;

FIG. 6 is a perspective view of an alternative embodiment of a tube porthaving a plurality of tubular stems;

FIG. 7 is a perspective view of the sampling port of the containmentsystem depicted in FIG. 1;

FIG. 8 is a cross sectional side view of the sampling port shown in FIG.7, with a temperature probe partially inserted therein;

FIG. 9 is a side view of the sampling port shown in FIG. 7, connected toa plurality of collection containers via a collection tube and amanifold;

FIG. 10 is a cross sectional side view of a portion of an alternativeembodiment of a sampling port;

FIG. 11 is an exploded perspective view of the sampling port shown inFIG. 10;

FIG. 12 is a cross sectional side view of another alternative embodimentof a sampling port;

FIG. 13A is a cross sectional side view of yet another alternativeembodiment of a sampling port;

FIG. 13B is a cross sectional end view of the sampling port shown inFIG. 13a taking along a line defined by 13B-13B;

FIG. 14A is a cross sectional side view of yet another alternativeembodiment of a sampling port;

FIG. 14B is a cross sectional end view of the sampling port shown inFIG. 14A taking along a line defined by 14B-14B; and

FIG. 15 is a cross sectional side view of yet another alternativeembodiment of a sampling port containing no sampling tube.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to tube ports and sampling ports as wellas container boa systems that incorporate such ports. In general, thetube ports of the present invention include a flexible tubular stem witha flange encircling and radially outwardly projecting from the stem. Thesampling ports of the present invention include an elongated flexiblesupport tube and an elongated flexible sampling tube each coupledtogether at a mounting location on a body. A flange encircles andradially outwardly projects from the support tube and the sampling tube.

The inventive tube ports and sampling ports can be used in bioreactorswhere it is necessary to mount probes, delivery and remove growth mediaand other components, and conduct sampling. However, the inventive tubeports and sampling ports can also be used in fermentation systems andother fluid processing, transport, and/or storage systems or the like.

As a result of using a flexible, tubular stem and flange, selectembodiments of the inventive tube ports have a variety of uniquebenefits over conventional rigid tube ports. By way of example and notby limitation, the inventive tube ports are relatively inexpensive tomake and are very flexible, allowing them to be used more easily withflexible containers. For example, due to the flexibility of the tubeports, the tube ports can be connected to flexible bags and otherstructures using methods and systems that cannot be used with rigid tubeports. The tube ports can also be easily scaled for use in smalllaboratory experiments or large scale commercial production systems.

The inventive tube ports can be formed as part of a flexible container,such as a disposable bag or liner, or can be coupled to such flexiblecontainers. The tube ports and related container can then besimultaneously sterilized and sold as a unitary system. This approachsimplifies the sterilization process. Furthermore, the entire tube portis designed to be soft and flexible so that the combined tube port andcontainer can be folded and/or rolled into a compact shape for storageand/or transport without risk of damage to the tube port or container.Numerous other advantages of different embodiments of the presentinvention will be discussed below or will be apparent from the followingdisclosure and appended drawings.

Depicted in FIG. 1 is one embodiment of a containment system 10incorporating features of the present invention. Containment system 10comprises a substantially rigid support housing 12 in which a containersystem 30 is disposed. Support housing 12 has an upper end 14, a lowerend 16, and an interior surface 18 that bounds a compartment 20. Formedat lower end 16 is a floor 22 and sidewalls 23 extend up from floor 22toward upper end 14. One or more openings 24 can extend through floor 22or sidewall 23 of container system 30 so as to communicate withcompartment 20. Upper end 14 terminates at a lip 26 that bounds anaccess opening 28 to compartment 20. If desired, a cover, not shown, canbe mounted on upper end 14 so as to cover access opening 28. It isappreciated that support housing 12 can come in a variety of differentsizes, shapes, and configurations. For example, in one alternativeembodiment access opening 28 can be closed by a permanent top end wall.An access port can be formed at another location on support housing 12such as the sidewall or floor. The access port can be selectively closedby a door.

As also depicted in FIG. 1, container system 30 is at least partiallydisposed within compartment 20 of support housing 12. Container system30 comprises a container 32 having one or more tube ports 33 which willbe described in more detail below. In the embodiment depicted container32 comprises a flexible bag-like body 36 having an interior surface 38that bounds a chamber 40 suitable for holding a fluid 41 or other typeof material. More specifically, body 36 comprises a side wall 42 that,when body 36 is unfolded, has a substantially circular or polygonaltransverse cross section that extends between a first end 44 and anopposing second end 46. First end 44 terminates at a top end wall 48while second end 46 terminates at a bottom end wall 50.

Body 36 is comprised of a flexible, water impermeable material such as alow-density polyethylene or other polymeric sheets having a thickness ina range between about 0.1 mm to about 5 mm with about 0.2 mm to about 2mm being more common. Other thicknesses can also be used. The materialcan be comprised of a single ply material or can comprise two or morelayers which are either sealed together or separated to form a doublewall container. Where the layers are sealed together, the material cancomprise a laminated or extruded material. The laminated materialcomprises two or more separately formed layers that are subsequentlysecured together by an adhesive.

The extruded material comprises a single integral sheet that comprisestwo or more layers of different material that can be separated by acontact layer. All of the layers are simultaneously co-extruded. Oneexample of an extruded material that can be used in the presentinvention is the Thermo Scientific CX3-9 film available from ThermoFisher Scientific. The CX3-9 film is a three-layer, 9 mil cast filmproduced in a cGMP facility. The outer layer is a polyester elastomercoextruded with an ultra-low density polyethylene product contact layer.Another example of an extruded material that can be used in the presentinvention is the Thermo Fisher CX5-14 cast film also available fromThermo Fisher Scientific. The Thermo Fisher CX5-14 cast film comprises apolyester elastomer outer layer, an ultra-low density polyethylenecontact layer, and an EVOH barrier layer disposed therebetween. In stillanother example, a multi-web film produced from three independent websof blown film can be used. The two inner webs are each a 4 mil monolayerpolyethylene film (which is referred to by Thermo Fisher Scientific asthe BM1 film) while the outer barrier web is a 5.5 mil thick 6-layercoextrusion film (which is referred to by Thermo Fisher Scientific asthe BX6 film).

The material is approved for direct contact with living cells and iscapable of maintaining a solution sterile. In such an embodiment, thematerial can also be sterilizable such as by ionizing radiation.Examples of materials that can be used in different situations aredisclosed in U.S. Pat. No. 6,083,587 which issued on Jul. 4, 2000 andUnited States Patent Publication No. US 2003-0077466 A1, published Apr.24, 2003 which are each hereby incorporated by specific reference.

In one embodiment, body 36 comprises a two-dimensional pillow style bagwherein two sheets of material are placed in overlapping relation andthe two sheets are bounded together at their peripheries to forminternal chamber 40. Alternatively, a single sheet of material can befolded over and seamed around the periphery to form internal chamber 40.In another embodiment, body 36 can be formed from a continuous tubularextrusion of polymeric material that is cut to length and the endsseamed closed.

In still other embodiments, body 36 can comprise a three-dimensional bagthat not only has an annular side wall but also a two-dimensional topend wall 48 and a two-dimensional bottom end wall 50. Three-dimensionalbody 36 comprises a plurality of discrete panels, typically three ormore, and more commonly four or six. Each panel is substantiallyidentical and comprises a portion of the side wall, top end wall, andbottom end wall of body 36. Corresponding perimeter edges of each panelare seamed. The seams are typically formed using methods known in theart such as heat energies, RF energies, sonics, or other sealingenergies.

In alternative embodiments, the panels can be formed in a variety ofdifferent patterns. Further disclosure with regard to one method ofmanufacturing three-dimensional bags is disclosed in United StatesPatent Publication No. US 2002-0131654 A1 that was published Sep. 19,2002 of which the drawings and Detailed Description are herebyincorporated by reference.

It is appreciated that body 36 can be manufactured to have virtually anydesired size, shape, and configuration. For example, body 36 can beformed having chamber 40 sized to 10 liters, 30 liters, 100 liters, 250liters, 500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000liters, 5,000 liters, 10,000 liters or other desired volumes. Althoughbody 36 can be any shape, in one embodiment body 36 is specificallyconfigured to be complementary or substantially complementary tocompartment 20 of support housing 12.

In any embodiment, however, it is desirable that when body 36 isreceived within compartment 20, body 36 is uniformly supported bysupport housing 12. Having at least generally uniform support of body 36by support housing 12 helps to preclude failure of body 36 by hydraulicforces applied to body 36 when filled with fluid.

Although in the above discussed embodiment container 32 has a flexible,bag-like configuration, in alternative embodiments it is appreciatedthat container 32 can comprise any form of collapsible container orsemi-rigid container. Furthermore, in contrast to having a closed topend wall 48, container 32 can comprise an open top liner. Container 14can also be transparent or opaque and can have ultraviolet lightinhibitors incorporated therein.

Mounted on side walls 42 and top end wall 48 are a plurality of tubeports 33 which are in fluid communication with chamber 40. Although fourtube ports 33 are shown, it is appreciated that one, two, three, or moretube ports 33 can be present depending on the intended use of container32. As such, each tube port 33 can serve a different purpose dependingon the type of processing to be undertaken. For example, tube ports 33can be coupled with a tube, such as fluid line 52, for dispensing fluidor other components into chamber 40 or withdrawing fluid from chamber40. In addition, such as when container 32 is used as a bioreactor forgrowing cells or microorganisms, tube ports 33 can be used to providevarious probes such as temperature probes, pH probes, dissolved oxygenprobes, and the like, access to chamber 40.

In general, each tube port 33 comprises a tubular stem 56 with a flange58 encircling and radially outwardly projecting from tubular stem 56.Turning to FIG. 2, stem 56 of tube port 33 has an interior surface 60and an opposing exterior surface 62 each extending between a first end64 and a longitudinally spaced apart second end 66. Interior surface 60bounds a passage 68 that longitudinally extends through stem 56.Interior surface 60 and/or exterior surface 62 can contain barbs orother protrusions extending therefrom or, as in the embodiment depicted,can be substantially smooth. One or both of interior surface 60 andexterior surface 62 can also have a constricting taper extending alongthe length thereof.

Flange 58 encircles stem 56 at first end 64 and radially outwardlyprojects therefrom. In the embodiment depicted, flange 58 has asubstantially circular configuration. In alternative embodiments, flange58 can be any other desired shape such as elliptical, square, or otherpolygonal or irregular configurations. Flange 58 has a first side 70 andan opposing second side 72 that each extend out to a perimeter edge 74.

Stem 56 and flange 58 can be molded as a unitary integral piece.Alternatively, stem 56 can be connected to flange 58 by welding usingconventional welding techniques such as heat welding, RF energy,ultrasonic, and the like or by using adhesives or any other conventionalattaching or fastening techniques.

Turning to FIG. 3, in one embodiment, an annular lip seal 76 radiallyinwardly projects from interior surface 60 of stem 56 so as to extendinto passage 68. Lip seal 76 is comprised of a first sidewall 78 and anopposing second sidewall 80 that extend from interior surface 60 to aninterior face 82. Although lip seal 76 can be disposed anywhere alonginterior surface 60, in the depicted embodiment lip seal 76 is disposedat first end 64 of stem 56 such that flange 58 and lip seal 76 aredisposed in substantially the same plane. Furthermore, first side 70 offlange 58 and first sidewall 78 of lip seal 76 are disposed insubstantially the same plane. Lip seal 76 is resiliently flexible so asto form an annular seal around a tube, probe, or other device to beinserted through passage 68, thereby preventing fluid or other materialsfrom entering or escaping chamber 40 of container 32 through passage 68.

For example, depicted in FIGS. 1 and 4 is a probe 84 having asubstantially cylindrical exterior surface 86 extending between aproximal end 87 and an opposing distal end 88. Probe 84 can comprise adissolved oxygen probe or any other type of probe such as a pH probe,temperature probe, or the like. Prior to filling container 32 with afluid, distal end 88 of probe 84 is advanced through tubular stem 56 oftube port 33 and past lip seal 76 so that distal end 88 projects freelyinto chamber 40 of container 32. As probe 84 passes lip seal 76, lipseal 76 outwardly flexes so as to resiliently bias against exteriorsurface 86 probe 84. As a result, a sealed engagement is formed betweenlip seal 76 and exterior surface 86 probe 84. This sealed engagementprevents any fluid or other material from entering or existing chamber40 through tubular stem 66. It thus prevents any material from beingcaught in a dead space 89 formed between probe 84 and the interiorsurface of stem 56.

The foregoing embodiment has the advantage that probe 84 can be easilyattached to container 32 by sealed engagement and can be easily removedfor subsequent sterilization and reuse. In turn, container 32 can bedisposed of after a single use so as to minimize cleaning andsterilization. It is appreciated that a variety of other sealing andconnecting structures can also be used in connecting probe 84 to tubeport 33 and container 32 so as to ensure that probe 84 is sterile whenentering container 32. Examples of such connection systems are disclosedin U.S. Pat. No. 7,384,783, issued Jun. 10, 2008 that is herebyincorporated herein by specific reference.

Returning to FIG. 3, when flange 58 and lip seal 76 are disposed insubstantially the same plane, an annular channel 90 can be recessed onflange 58 to aid in the flexibility of lip seal 76. Channel 90 isbounded by a substantially c-shaped floor 92 that is recessed into firstside 70 of flange 58 so as to encircle lip seal 76 and the opening topassage 68. That is, channel 90 has an inside diameter that is slightlylarger than the inside diameter of passage 68 at first end 64 of stem56. Channel 90 decreases the surrounding support of lip seal 76 so thatlip seal 76 can more easily flex as probe 84 or other structure ispassed therethrough.

Lip seal 76 is comprised of a soft, flexible material and can be moldedfrom the same material as stem 56 and/or flange 58. Lip seal 76 can beseparately attached to tubular stem 56 in the same manner as previouslydiscussed with regard to flange 58 but is more commonly integrallyformed with stem 56 and flange 58. As such, tube port 33 is typicallymolded as a unitary integral member. In an alternative embodiment, it isappreciated that lip seal 76 can be eliminated from tube port 33 wheretube port 33 is not being used to receive a probe or other structure.

In one embodiment, tube port 33 is molded from a soft, resilientlyflexible polymeric material or elastomeric material such aspolyethylene, silicone or KRATON® having a durometer on a Shore A scalewith a value of less than 90 and more preferably less than 70 buttypically greater than 5. In other embodiments, other thermoset orthermoplastic polymers having a durometer in the above range can also beused. Other materials such as those previously discussed with regard tocontainer 32 can also be used. In some embodiments, as a result of thematerial properties, tubular stem 56 can be manually folded over so asto kink passage 68 closed or tubular stem 56 can be manually pinched,such as by a clamp, to close passage 68 wherein in each case tubularstem 56 will resiliently return to the original configuration withsubstantially no permanent deformation.

In one embodiment, flange 58 has a maximum diameter typically in a rangebetween about 2 cm to about 30 cm with about 5 cm to about 15 cm beingmore common. Stem 56 typically has a length in a range between about 2cm to about 30 cm with about 5 cm to about 15 cm being more common.Likewise, stem 56 typically has a maximum inner diameter in a rangebetween about 0.2 cm to about 5 cm with about 0.5 cm to about 3 cm beingmore common. In alternative embodiments, it is appreciated that each ofthe above dimensions can be varied. For example, if desired stem 56 cancomprise an elongated tube having a length of one meter or longer. It isfurther noted that in the present embodiment second end 66 of tubularstem 56 has a smooth, substantially cylindrical configuration oninterior surface 60 and exterior surface 62 with no flanges, barbs, orother projections extending therefrom.

One of the benefits of tube port 33 is that it is more easily adaptablefor coupling with tubes of different diameter or configuration. Forexample, it is envisioned that container system 30, which comprisescontainer 32 and tube port 33, could be sold to an end user as a singleunit. In turn, the established system of the end user may have a varietyof different sizes or types of hoses that would connect with stem 56 oftube port 33 for delivering gas, liquid, or other material thereto orfor retrieving material from the container. As a result of flexible stem56, only a single coupler having opposing ends with predefined sizeswould be needed to couple stem 56 to the hose.

For example, turning to FIG. 5, a tubular connector 94 is providedhaving an interior surface 96 and an opposing exterior surface 98 eachextending between a first end 100 and a longitudinally spaced apartsecond end 102. Interior surface 96 bounds a passage 106 thatlongitudinally extends through connector 94. Ends 100 and 102 both haveannular barbs 108 radially outwardly projecting therefrom. First end 100is secured within passage 68 at second end 66 of tubular stem 56.Tubular stem 56 resiliently constricts around connector 94 to form afluid tight seal therewith. A plastic pull tie 110 can also be securedaround the portion of second end 66 of tubular stem 56 disposed overconnector 94 so as to further secure the sealed engagement therebetween.Second end 102 of connector 94 is received within a first end 104 of afluid line 52.

In some embodiments, fluid line 52 has the same diameter as stem 56. Inthese embodiments, both ends of connector 94 are of equal diameter toeach other. If, however, fluid line 52 has a diameter different thanstem 56, a standard connector 94 can be provided with second end 102having a different size than first end 100. Second end 102 is configuredto couple with fluid line 52, as shown in the embodiment depicted.

In contrast, if a conventional rigid barbed stem were formed on flange58, it would be necessary to first couple a tube to the barbed stem andthen use connector 94 to account for the change in size of fluid line52. As a result, stem 56 provides for a more universal connection.Furthermore, as a result of flange 58 and stem 56 both being comprisedof a soft and flexible material, container 32 can be folded and/orrolled up for transport and/or storage without fear of damage to tubeports 33 and/or container 32.

Depicted in FIG. 6 is a tube port 150 according to an alternativeembodiment of the current invention wherein like elements between tubeports 33 and 150 are identified by like reference characters. Tube port150 comprises a plurality of tubular stems 56 a-c projecting from secondside 72 of flange 58. Each stem 56 a-c has a passage 68 extendinglongitudinally therethrough and being connected to flange 58 asdescribed above with reference to tube port 33. Although three stems 56a-c are shown, it is appreciated that two, or four or more stems canalternatively be used with the same flange. Each stem 56 a-c can be ofthe same diameter or length as the other stems or all the stems can besized differently from each other or some combination thereof. One ofthe benefits of having multiple tubular stems on tube port 150 is thatit allows different sizes of connectors 118 to be used when connectingwith various fluid lines 52. When a stem is not in use, a clamp 112 canbe removably closed across the stem so as to seal closed the passageextending therethrough. It is appreciated that clamp 112 can comprise ahose clamp or a variety of other types of clamps.

Returning to FIG. 1, mounted on side wall 42 is a sampling port 200which is in fluid communication with chamber 40. Although only onesampling port 200 is shown, it is appreciated that two or more samplingports 200 can be present depending on the intended use of container 32.As such, each sampling port 200 can serve a different purpose dependingon the type of processing to be undertaken. For example, each samplingport 200 can be coupled with an external container (see, e.g., FIG. 9)to deposit fluid or other material withdrawn from chamber 40 or toretrieve fluid or other material to insert into chamber 40. In addition,such as when container 32 is used as a bioreactor for growing cells ormicroorganisms, sampling ports 200 can simultaneously be used to providevarious probes, such as temperature probes, and the like, access tochamber 40 without being contaminated by the material within chamber 40.In one embodiment, sampling port 200 comprises an elongated flexiblesupport tube 202 and an elongated flexible sampling tube 204 eachcoupled to a body 206, with a flange 208 encircling and radiallyoutwardly projecting from body 206.

Turning to FIG. 7, body 206 of sampling port 200 has a generallycylindrical shape with an exterior surface 210 extending between a firstend face 212 and an opposing second end face 214. Body 206 bounds afirst passage 216 and a second passage 218 each extending between firstend face 212 and second end face 214. In one embodiment, first passage216 and second passage 218 extend in adjacent parallel alignment witheach other substantially the full length of body 206. In alternativeembodiments, exterior surface 210 of body 206 can have a variety ofalternative transverse cross sections such as elliptical or polygonal,or irregular.

Support tube 202 of sampling port 200 has an interior surface 220 and anopposing exterior surface 222 each extending between a first end 224 anda longitudinally spaced apart second end 226. Interior surface 220bounds a first passageway 228 that longitudinally extends throughsupport tube 202. First passageway 228 is open at second end 226 andclosed at first end 224. Closure of first end 224 can occur duringproduction or post production by heat sealing, clamping, or any otheravailable method.

Second end 226 of support tube 202 is coupled with first end face 212 ofbody 206 at a mounting location 230 so as to communicate with firstpassage 216 of body 206. In this manner, first passageway 228 of supporttube 202 and first passage 216 of body 206 combine to form a firstcontinuous passage 232 having a first end 234 at sealed first end 224 ofsupport tube 202 and a second end 236 at open second end face 214 ofbody 206.

In many embodiments, a probe or other rigid support can be inserted intofirst continuous passage 232. For example, as shown in FIG. 8, atemperature probe 238 having an exterior surface 240 has been partiallyinserted into first continuous passage 232 of sampling port 200. Whenfully inserted, a distal end 242 of temperature probe 238 is disposed ator near sealed first end 224 of support tube 202, which extends intochamber 40 of container 32. When a probe or rigid support is inserted,flexible support tube 202 becomes substantially rigid as it extends intochamber 40 of container 32 as a result of the rigidity of the inserteditem.

Because support tube 202 is sealed closed at first end 224, any probe orother support inserted into support tube 202 does not directly contactthe liquid or other material within chamber 40 of container 32. As aresult, probes or other rigid supports can be inserted and extractedfrom first continuous passage 232 without fear of any liquid or othermaterial leaking out of chamber 40 or becoming contaminated by probe238. Furthermore, because probe 238 does not contact the contents ofchamber 40, probe 238 can be repeatedly used without the need forsterilization or cleaning between uses.

Returning to FIG. 7, Similar to support tube 202, sampling tube 204 ofsampling port 200 has an interior surface 244 and an opposing exteriorsurface 246 each extending between a first end 248 and a longitudinallyspaced apart second end 250. Interior surface 244 bounds a secondpassageway 252 that longitudinally extends through sampling tube 204.Second passageway 252 is open at second end 250 and, unlike firstpassageway 228, open at first end 248, thus allowing fluid communicationcompletely through sampling tube 204. Second end 250 of sampling tube204 is coupled with first end face 212 of body 206 at mounting location230 so as to communicate with second passage 218 of body 206. In thismanner, second passageway 252 of sampling tube 204 and second passage218 of body 206 combine to form a second continuous passage 254 having afirst end 256 at open first end 248 of sampling tube 204 and a secondend 258 at open second end face 214 of body 206, allowing fluidcommunication therethrough.

At least a portion of sampling tube 204 extends along support tube 202in adjacent parallel alignment with first end 248 of sampling tube 204being disposed at or toward first end 224 of support tube 202. In theembodiment depicted, sampling tube 204 is in adjacent parallel alignmentwith support tube 202 along the entire length of sampling tube 204. Tofacilitate a parallel alignment, sampling tube 204 is coupled withsupport tube 202 along the entire length of sampling tube 204. Inalternative embodiments, sampling tube 204 can be coupled to supporttube 202 at spaced apart locations. As a result of this coupling, when arigid probe or support is inserted into support tube 202, as describedpreviously, sampling tube 204 also becomes substantially rigid as itextends into chamber 40 of container 32.

In the embodiment depicted, sampling tube 204 is of a smaller diameterthan support tube 202. It is appreciated that in alternativeembodiments, sampling tube 204 can have a larger diameter than or havethe same diameter as support tube 202. Sampling tube 204 and supporttube 202 each have a length in a range typically between about 2 cm toabout 40 cm with about 5 cm to about 25 cm being more common. Otherlengths can also be used.

Flange 208 encircles body 206 at mounting location 230 and radiallyoutwardly projects therefrom. In the embodiment depicted, flange 208 hasa substantially circular configuration. In alternative embodiments,flange 208 can be any other desired shape such as elliptical, square, orother polygonal or irregular configurations. Flange 208 has a first side260 and an opposing second side 262 that each extend out to a perimeteredge 264. Support tube 202, sampling tube 204, body 206, and flange 208can be molded as a unitary integral piece. Alternatively, support tube202 and sampling tube 204 can be connected to each other and/or to body206 by welding using conventional welding techniques such as heatwelding, RF energy, ultrasonic, and the like or by using adhesives otherany other conventional attaching or fastening techniques.

In some embodiments, an elongated collection tube 266 extends outwardfrom second end face 214 of body 206. Collection tube 266 has aninterior surface 268 and an opposing exterior surface 270 each extendingbetween a first end 272 and a longitudinally spaced apart second end274. Interior surface 268 bounds a third passageway 276 thatlongitudinally extends through collection tube 266. Third passageway 276is open at first end 272 and second end 274, thus allowing fluidcommunication completely through collection tube 266. First end 272 ofcollection tube 266 is coupled with second end face 214 of body 206 soas to communicate with second passage 218. Thus, because secondpassageway 252 and second passage 218 are in fluid communication witheach other as described previously, second passageway 252 of samplingtube 204, second passage 218 of body 206, and third passageway 276 ofcollection tube 266 combine to form a third continuous passage 278through which fluid can flow between first end 248 of sampling tube 204to second end 274 of collection tube 266 in either direction. Andbecause first end 248 of sampling tube 204 and second end 274 ofcollection tube 266 are both open, fluid can flow externally of thirdcontinuous passage 278.

Turning to FIG. 9, in many embodiments, second end 274 of collectiontube 266 is attached to one or more collection containers 280 to storefluid or other material that has been collected from within chamber 40of container 32. Alternatively, collection tube 266 can be used toretrieve fluid or other material from collection containers 280 toinsert into chamber 40. Although the embodiment depicted displayscollection tube 266 connected to a manifold 282, which is connected to aplurality of collection containers 280, it is appreciated thatcollection tube 266 can be attached directly to a single collectioncontainer 280, bypassing manifold 282. Collection containers 280 can beany standard containers known in the art for use in such systems buttypically comprise sterile plastic bags.

In one embodiment, sampling port 200 is molded from a soft, resilientlyflexible polymeric material or elastomeric material such aspolyethylene, silicone or KRATON® having a durometer on a Shore A scalewith a value of less than 90 and more preferably less than 70 buttypically greater than 5. In other embodiments, other thermoset orthermoplastic polymers having a durometer in the above range can also beused. Other materials such as those previously discussed with regard tocontainer 32 can also be used. In some embodiments, as a result of thematerial properties, support tube 202 and sampling tube 204 can bemanually folded over so as to kink the passages therein closed orsupport tube 202 and sampling tube 204 can be manually pinched, such asby a clamp, to close the passages therein without significant permanentdeformation to support tube 202 or sampling tube 204.

As described previously, in many embodiments support tube 202, samplingtube 204, flange 208, and body 206 are all molded to be a single unitaryintegral piece. However, it is appreciated that all or some of theelements of the sampling port can alternatively be discrete componentsthat are connected, attached, or otherwise biased together to form thesampling port. For example, depicted in FIGS. 10 and 11 is analternative embodiment of a sampling port 300 wherein common featuresbetween sampling port 200 and sampling port 300 are identified by likereference characters. With reference to FIG. 11, sampling port 300comprises a tube assembly 305 and tube port 33 as previously discuss.

Tube assembly 305 includes a substantially cylindrical body 301 that issubstantially the same as body 206 except that body 301 is sized andshaped to snugly fit within stem 56 of tube port 33. For example, in theembodiment depicted, body 301 has a taper extending along the entirelength of body 301 that substantially matches a taper of interiorsurface 60 of stem 56. Support tube 202 and sampling tube 204 projectfrom first end face 212 of body 301 while collection tube 266 projectsfrom second end face 214 of body 301.

During assembly, support tube 202 and sampling tube 204 are advancedthrough stem 56 of tube port 33. Tube port 33 is advanced over body 301until second end 66 butts against an annular shoulder 307 outwardlyprojecting from the second end of body 301. As depicted in FIG. 10, inthis position lip seal 76 radially biases against exterior surface 303of body 301 at the first end thereof so as to form a sealed engagementtherebetween. To provide a more secure engagement and seal between stem56 and body 301, one or more pull ties, clamps, or other tighteningdevices can be used. For example, in the embodiment depicted a plasticpull tie 302 is secured around the portion of second end 66 of tubularstem 56 disposed over body 301 so as to further secure the sealedengagement therebetween.

To keep one or both of passages 216 or 218 from collapsing under theforce of pull tie 302, a rigid sleeve 308 made of metal or other rigidmaterial can be inserted into first passage 216 prior to tightening pulltie 302. Pull tie 302 is positioned so as to be disposed over sleeve308. Sleeve 308 is disposed within first passage 216 because firstpassage 216 has a larger diameter than second passage 218 and thus canmore easily collapse. Where the diameter of second passage 218 isincreased, a second rigid sleeve 308 can also be positioned therein. Itis appreciated that other types of tightening devices can be usedalternatively or in conjunction with pull tie 302. After pull tie 302 ispositioned, the assembled sampling port 300 can be secured to container32 by welding flange 58 to container 32 using conventional weldingtechniques. The entire assembly can then be sterilized using radiationor other types of sterilization. During use, temperature probe 238 orother rigid device can then be inserted into support tube 202, ifdesired.

It is appreciated that the sampling ports can come in a variety of otheralternative configurations. For example, depicted in FIG. 12 is analternative embodiment of a sampling port 320 incorporating features ofthe present invention. Common features between sampling port 200 andsampling port 320 are identified by like reference characters. Forexample, sampling port 320 comprises an elongated flexible support tube202, an elongated flexible sampling tube 204, and a flange 208. However,in contrast to sampling port 200, sampling port 320 does not have abody. Instead, flange 208 simply encircles and radially outwardlyprojects from support tube 202 and sampling tube 204 at a mountinglocation 322. Support tube 202 and sampling tube 204 can be coupledtogether at discrete locations or along their entire length. If acollection tube is used, collection tube 266 extends outward from secondend 250 of sampling tube 204 at mounting location 322 such that thirdpassageway 276 of collection tube 266 fluidly communicates with secondpassageway 252 of sampling tube 204.

Depicted in FIGS. 13A-B is another alternative embodiment of a samplingport 330 incorporating features of the present invention. Like elementsbetween sampling port 200 and sampling port 330 are identified by likereference characters. Instead of having discrete support and samplingtubes as in sampling port 200, sampling port 330 has an elongatedflexible member 332 having two separate passages enclosed therein.Flexible member 332 has an exterior surface 334 extending between afirst end 336 and an opposing second end 338. Member 332 bounds a firstpassageway 340 and a second passageway 342 each extending between firstend 336 and second end 338. Similar to first passageway 228 of supporttube 202 of sampling port 200, first passageway 340 of sampling port 330is open at second end 338 and closed at first end 336. Similar to secondpassageway 252 of sampling tube 204 of sampling port 200, secondpassageway 342 of sampling port 330 is open at first end 336 and secondend 338. Although not depicted as such, sampling port 330 may alsoinclude a body 206 similar to sampling port 200.

If a collection tube is used, collection tube 266 extends outward fromsecond end 338 of member 332 such that third passageway 276 ofcollection tube 266 fluidly communicates with second passageway 342 ofmember 332. Of course, as with all embodiments having a collection tube,the second end 274 of collection tube 266 can be connected to one ormore collection containers 280, as previously discussed.

First passageway 340 and second passageway 342 can have a number ofdifferent configurations. For example, in the embodiment depicted, firstpassageway 340 and second passageway 342 are in adjacent parallelalignment with each other. Alternatively, as shown in FIGS. 14A-B,second passageway 342 can radially encircle first passageway 340 atfirst end 336 of flexible member 332, but not necessarily encircle firstpassageway 340 at second end 338. Specifically, FIGS. 14A-B depict aprobe port 360 that includes member 332 that projects from flange 208.At least a portion of tubular member 332 comprises a tubular outersleeve 364 and a tubular inner sleeve 366 disposed within outer sleeve364. Inner sleeve 366 bounds first passageway 340 extending along alength of the inner sleeve 266. It is appreciated that many otherconfigurations are also possible. Regardless of the configuration, inthe depicted embodiments first passageway 340 is closed at first end 336and second passageway 342 is open at first end 336. It is also desirablefor first passageway 340 to be able to be aligned in a straight line soas to accommodate a rigid temperature probe or the like.

Depicted in FIG. 15 is one embodiment of a probe port 350 using tubeport 33 and incorporating features of the present invention. Likeelements between sampling port 300 and probe port 350 are identified bylike reference characters. Probe port 350 comprises a body 352 that issimilar to body 301 (FIG. 10) except that second passage 218 has beenremoved. Support tube 202 connects to and projects from body 352 so asto communicate with first passage 216. Tube port 33 couples with body352 in the same manner that tube port 33 coupled with body 301. In thisembodiment, a probe, such as a temperature probe, can be inserted intosupport tube 202 of probe port 350 to monitor conditions within chamber40 without the probe being contaminated by any material within chamber40. However, unlike sampling port 300, no sampling of material fromwithin chamber 40 can be performed using probe port 350.

It is appreciated that the various sampling ports have many of the sameadvantages as previously discussed with regard to the tube port. For thesampling ports are inexpensive to manufacture, disposable, scalable, andcan be rolled up and folded within container 32 during manufacture,sterilization, storage and transport without risk of damage to container32 or the sampling port. Other advantages have been discussed herein orare readily apparent from the design.

Returning to FIGS. 1 and 5, extending through side wall 42 of container32 are a number of holes 54. Each hole 54 is aligned with acorresponding opening 24 on sidewall 23 of support housing 12. A portionof a tube port 33 or a sampling port 200 according to variousembodiments of the present invention extends through each one of theholes 54 and openings 24. Each tube port 33 or sampling port 200 issealed to body 36 of container 32 so that fluid cannot leak out throughhole 54.

For each tube port 33, second surface 72 of flange 58 is sealed tosidewall 42 of container 32 so as to secure tube port 33 to container 32and to prevent liquid or other material from leaking out through hole54. Flange 58 is typically secured to container 32 by conventionalwelding techniques. Alternatively, however, adhesives or mechanicalconnections can also be used.

Similar to flange 58 of each tube port 33, first side 260 of flange 208is sealed to sidewall 42 of container 32 for each sampling port 200 soas to secure sampling port 200 to container 32 and to prevent liquid orother material from leaking out through hole 54. Flange 208 is typicallysecured to container 32 by conventional welding techniques.Alternatively, however, adhesives or mechanical connections can also beused. If a tube port 33 is used in conjunction with a sampling port(see, e.g., sampling port 300 of FIGS. 10 and 11), flange 58 of tubeport 33 is sealed to sidewall 23 as described previously, then body 301and/or support and sampling tubes 202 and 204 are inserted throughpassage 68 of stem 56 until exterior surface 303 of body 301 biasesagainst interior surface 60 of tubular stem 56, creating a liquid tightseal. It is appreciated that flange 58 alternatively can be sealed tosidewall 42 after body 301 has been inserted through passage 68.

Once container system 30 is fully assembled, the system can be sealedwithin a storage bag and the entire system sterilized such as throughvarious forms of radiation sterilization.

During operation, container system 30 is positioned within compartment20 of support housing 12 so that stems 56 of tube ports 33 and bodies206 and/or support and sampling tubes 202 and 204 of sampling ports 200pass through openings 24 in support housing 12.

For each tube port 33, a tube, such as fluid line 52, is then coupledwith stem 56 using connector 118 as previously discussed, or a probe 84,such as temperature probe, a dissolved oxygen probe, or the like, isinserted through stem 56 into chamber 40 of container 32, so that asubstantially liquid tight seal is formed between an exterior surface ofconnector 118 or probe 84 and stem 56.

Next, a fluid 41 is dispensed into chamber 40 of container 32 by way ofports 33 which are coupled to input fluid lines 52. Fluid 41 cancomprise a variety of different materials. For example, where containersystem 30 is being used as a bioreactor for growing cells ormicroorganisms, fluid 41 can comprise a growth media that is dependentupon the type of cells or microorganism being cultured. The fluid canalso include a seed inoculum such as bacteria, fungi, algae, plantcells, animal cells, protozoans, nematodes, or the like. The presentinvention can also be used for non-biological systems. For example, thesystem can be used for processing or mixing solutions where it isdesired to control or regulate the pH or partial pressure of gas withina solution. The fluid is prevented from leaking out of chamber 40 by wayof the substantially liquid tight seals formed between connectors 118 orprobes 84 and stems 56, as discussed previously.

For each sampling port 200, a probe, such as temperature probe 238 orother type of rigid support, is inserted into first continuous passage232 of sampling port 200, as discussed previously. Because support tube202 is sealed closed at first end 224, probes or other types of rigidsupports can be inserted and extracted using sampling port 200 whileliquid or other material remains within chamber 40 while preventing anymaterial to leak out of chamber 40.

Various parameters within chamber 40 of container 32 are measured by theprobes that have been inserted into chamber 40 using tube ports 33 andsampling ports 200. These parameters can include temperature, pressurelevels, and the like and can be measured once, periodically,continuously, or in any other known manner.

When desired, material is removed from chamber 40 of container 32 usingsampling tubes 204 of sampling ports 200 which are coupled to collectiontubes 266. When a rigid support or probe has been inserted into supporttube 202, the rigid probe or support allows sampling tube 204 to extendrelatively rigidly into chamber 40 due to the coupling between supporttube 202 and sampling tube 204, discussed previously. This allowssampling tube 204 to retrieve the sample from deeper within chamber 40,further away from the interior surface 38 of container 32 than would beallowed otherwise. This gives a more representative sample of thematerial within chamber 40. Once retrieved, the material is thendeposited in one or more collection containers 280 for furtherprocessing, as discussed previously.

As previously mentioned, the illustrative container system 10 depictedin FIG. 1 is generally configured as a bioreactor for growing cells ormicroorganism. To that end, a sparger 34 is mounted on container 32 fordelivering controlled gases to growth media that is disposed withincontainer 32. Further disclosure with regard to sparger 34 is disclosedin U.S. Pat. No. 7,384,783, issued Jun. 10, 2008 that was previouslyincorporated herein by specific reference and United States PublicationNo. 2006/0270036, published Nov. 30, 2006 which is incorporated hereinby specific reference.

In one embodiment it is noted that sparger 34 can be formed by securinga gas permeable sparger material to flange 58 of tube port 33 so that bydelivering a gas though stem 56, the gas is forced to travel out throughthe gas permeable sparger material. Further disclosure with regard tothe types of materials that can be used for the gas permeable spargermaterial and how to attach it to flange 58 are also disclosed in theabove referenced Publication No. 2006/0270036.

Although not required, in one embodiment means are also provided formixing fluid within chamber 40. By way of example and not by limitation,in one embodiment a drive shaft 114 projects into chamber 40 and has animpeller 116 mounted on the end thereof. External rotation of driveshaft 114 thus facilitates rotation of impeller 116 which mixes and/orsuspends fluid within chamber 40. Sparger 34 is typically disposeddirectly below the means for mixing such that the mixing or movement ofthe fluid produced by the mixer helps to entrain the gas bubbles withinthe fluid. One specific example of how to incorporate a rotational mixerinto a flexible container is disclosed in U.S. Patent Publication No. US2005/0239199, published Oct. 27, 2005 which is incorporated herein byspecific reference. Another example is disclosed in U.S. ProvisionalPatent Application No. 60/784,403, filed Mar. 20, 2006, entitled MixingSystems and Related Mixers in the names of Whitt F. Woods et al. whichhas been published as US Publication No. 2006/0280028, on Dec. 14, 2006,and which are incorporated herein by specific reference.

In an alternative embodiment of the means for mixing, mixing can beaccomplished by vertically reciprocally moving a vertical mixer withinchamber 40. Further disclosure with regard to the assembly and operationof a vertical mixer is disclosed in U.S. Publication No. 2006/0196501,published Sep. 7, 2006, which is incorporated herein by specificreference. In yet other embodiments, it is appreciated that the mixingcan be accomplished by simply circulating fluid through chamber 40 suchas by using a peristaltic pump to move fluid in and out of chamber 40.Other conventional mixing techniques can also be used.

It is appreciated that the foregoing embodiments are simply examples ofalternative methods of forming tube ports or sampling ports of thepresent invention. It is likewise appreciated that the various featuresof the different embodiments can be mixed and matched to produce stillother embodiments.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed is:
 1. A container system comprising: a flexible bagbounding a chamber; and a port comprising: an elongated tubular memberhaving an interior surface bounding a first passageway extending betweena first end and an opposing second end, the elongated tubular memberbeing comprised of a polymeric or elastomeric material and beingflexible; and a flange coupled to the elongated tubular member andradially outwardly projecting therefrom, the flange being welded orotherwise permanently secured to the flexible bag so that the first endof the elongated tubular member projects into the chamber of theflexible bag while the second end of the first passageway of theelongated tubular member is accessible from outside of the flexible bag.2. The container system as recited in claim 1, wherein the firstpassageway of the elongated tubular member is closed at the first end.3. The container system as recited in claim 1, wherein the flange iscircular and radially outwardly projects at the second end of theelongated tubular member.
 4. The container system as recited in claim 1,wherein the flange encircles the elongated tubular member.
 5. Thecontainer system as recited in claim 1, wherein the elongated tubularmember has a durometer on a Shore A scale with a value of less than 90.6. The container system as recited in claim 1, wherein the elongatedtubular member has a durometer on a Shore A scale with a value of lessthan
 70. 7. The container system as recited in claim 1, wherein theelongated tubular member is flexible to enable the elongated tubularmember to be folded over upon itself so as to kink the first passagewayclosed with substantially no permanent deformation to the elongatedtubular member.
 8. The container system as recited in claim 1, whereinthe flange and the elongated tubular member are integrally moldedtogether as a single unitary member.
 9. The container system as recitedin claim 1, wherein the flange and the elongated tubular member areseparate members that are removably coupled together.
 10. The containersystem as recited in claim 1, wherein the port further comprises a tubeport removably coupled with the elongated tubular member, the tube portcomprising: a tubular stem having an interior surface bounding a passageextending therethrough, the elongated tubular member being coupled tothe tubular stem; and the flange encircling and radially outwardlyprojecting from the tubular stem.
 11. The container system as recited inclaim 1, further comprising a rigid sleeve disposed within the firstpassageway of the elongated tubular member.
 12. The container system asrecited in claim 1, wherein the port is configured to receive adissolved oxygen probe, a pH probe, or a temperature probe.
 13. Thecontainer system as recited in claim 1, further comprising a rigidsupport housing bounding a compartment, the flexible bag being disposedwithin the compartment of the rigid support housing, the rigid supporthousing having an opening extending therethrough that is aligned withthe port so that the port is disposed within the opening of the supporthousing.
 14. The container system as recited in claim 1, furthercomprising a fluid housed within the chamber of the flexible bag, thefluid comprising a media and cells or microorganisms to be culturedtherein.
 15. A container system comprising: a flexible bag bounding achamber; and a port comprising: an elongated tubular member extendingbetween a first end and an opposing second end, at least a portion ofthe elongated tubular member comprising a tubular outer sleeve and atubular inner sleeve disposed within the tubular outer sleeve, thetubular inner sleeve bounding a first passageway extending along alength of the tubular inner sleeve, at least portions of the tubularouter sleeve and the tubular inner sleeve being spaced apart so that asecond passageway is formed therebetween, the elongated tubular memberbeing comprised of a polymeric or elastomeric material and beingflexible; and a flange coupled to the elongated tubular member andradially outwardly projecting therefrom, the flange being secured to theflexible bag.
 16. The container system as recited in claim 15, whereinthe port projects into the chamber of the flexible bag.
 17. Thecontainer system as recited in claim 15, wherein the flange is circularand radially outwardly projects from the elongated tubular member. 18.The container system as recited in claim 15, wherein the flange and theelongated tubular member are integrally molded together as a singleunitary member.
 19. The container system as recited in claim 15, whereinthe tubular inner sleeve and the tubular outer sleeve are integrallymolded together as a single unitary member.
 20. The container system asrecited in claim 15, further comprising a rigid support housing boundinga compartment, the flexible bag being disposed within the compartment ofthe rigid support housing, the rigid support housing having an openingextending therethrough that is aligned with the port so that the port isdisposed within the opening of the support housing.
 21. The containersystem as recited in claim 15, wherein the elongated tubular member isflexible to enable the elongated tubular member to be folded over uponitself so as to kink the first passageway closed with substantially nopermanent deformation to the elongated tubular member.
 22. A containersystem comprising: a flexible bag bounding a chamber; and a portcomprising: an elongated tubular member extending between a first endand an opposing second end, at least a portion of the elongated tubularmember comprising a tubular outer sleeve and a tubular inner sleevedisposed within the tubular outer sleeve, the tubular inner sleevebounding a first passageway extending along a length of the tubularinner sleeve, the tubular inner sleeve and the tubular outer sleevebeing integrally molded together as a single unitary member, theelongated tubular member being comprised of a polymeric or elastomericmaterial and being flexible; and a flange coupled to the elongatedtubular member and radially outwardly projecting therefrom, the flangebeing secured to the flexible bag.